Noninfectious entry of HIV-1 into peripheral and brain macrophages mediated by the mannose receptor.

Proc Natl Acad Sci U S A

Molecular and Integrative Physiological Sciences, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA.

Published: March 2007

AI Article Synopsis

  • Although the role of protein receptors in HIV-1 infection is well understood, the interactions between cellular carbohydrate receptors, like the macrophage mannose receptor (MR), and HIV-1 are less clear.
  • HIV-1 can bind to and enter human and mouse macrophages via the MR, but this process does not lead to viral replication, indicating that MR allows entry without productive infection.
  • The study also found that HIV-1 gp120 can block the MR-mediated phagocytosis in macrophages, suggesting that understanding this non-infectious pathway might help in developing HIV-1 vaccines and improving knowledge of HIV/AIDS and the immune response.

Article Abstract

Although protein receptors on the plasma membrane involved in the initial steps of productive HIV-1 infection have been well characterized, little is known about interactions between cellular carbohydrate receptors and HIV-1. Here, we report the involvement of a carbohydrate receptor, the macrophage mannose receptor (MR), and its role in supporting HIV-1 binding and entry. HIV-1 can enter the cytoplasm of human macrophages and microglia as well as murine macrophages by MR, although no subsequent viral replication was observed. Correspondingly, HIV-1 entry into Cos-7 cells after induction of expression of MR by transfection with MR-cDNA did not demonstrate viral replication. Our studies suggest that whereas MR may serve as a binding and an entry site, the MR-mediated pathway does not lead to productive HIV-1 infection. In addition, we report that recombinant HIV-1 gp120 blocks MR-mediated phagocytosis in human and murine alveolar macrophages and microglial cells. Therefore, characterization of the HIV-1 noninfectious MR-mediated phagocytic pathway may foster advances in HIV-1 vaccine design and an improved understanding of HIV-1/AIDS pathogenesis and host defenses.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1821124PMC
http://dx.doi.org/10.1073/pnas.0611263104DOI Listing

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